Distribution and prognostic impact of microglia/macrophage subpopulations in gliomas.
Adult
Aged
Animals
Astrocytoma
/ pathology
Brain Neoplasms
/ pathology
Cell Line, Tumor
Female
Glioblastoma
/ pathology
Glioma
/ immunology
Humans
Immunohistochemistry
Macrophages
/ immunology
Male
Mice
Microglia
/ immunology
Middle Aged
Prognosis
Tumor Microenvironment
Xenograft Model Antitumor Assays
glioma
glioma-associated microglia and macrophages
immune polarization
tumor microenvironment
Journal
Brain pathology (Zurich, Switzerland)
ISSN: 1750-3639
Titre abrégé: Brain Pathol
Pays: Switzerland
ID NLM: 9216781
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
received:
06
08
2018
accepted:
14
11
2018
pubmed:
7
12
2018
medline:
13
2
2020
entrez:
4
12
2018
Statut:
ppublish
Résumé
While the central nervous system is considered an immunoprivileged site and brain tumors display immunosuppressive features, both innate and adaptive immune responses affect glioblastoma (GBM) growth and treatment resistance. However, the impact of the major immune cell population in gliomas, represented by glioma-associated microglia/macrophages (GAMs), on patients' clinical course is still unclear. Thus, we aimed at assessing the immunohistochemical expression of selected microglia and macrophage markers in 344 gliomas (including gliomas from WHO grade I-IV). Furthermore, we analyzed a cohort of 241 IDH1R132H-non-mutant GBM patients for association of GAM subtypes and patient overall survival. Phenotypical properties of GAMs, isolated from high-grade astrocytomas by CD11b-based magnetic cell sorting, were analyzed by immunocytochemistry, mRNA microarray, qRT-PCR and bioinformatic analyses. A higher amount of CD68-, CD163- and CD206-positive GAMs in the vital tumor core was associated with beneficial patient survival. The mRNA expression profile of GAMs displayed an upregulation of factors that are considered as pro-inflammatory M1 (eg, CCL2, CCL3L3, CCL4, PTGS2) and anti-inflammatory M2 polarization markers (eg, MRC1, LGMN, CD163, IL10, MSR1), the latter rather being associated with phagocytic functions in the GBM microenvironment. In summary, we present evidence that human GBMs contain mixed M1/M2-like polarized GAMs and that the levels of different GAM subpopulations in the tumor core are positively associated with overall survival of patients with IDH1R132H-non-mutant GBMs.
Identifiants
pubmed: 30506802
doi: 10.1111/bpa.12690
pmc: PMC6849857
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
513-529Informations de copyright
© 2018 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.
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